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St. John's wort (Hypericum perforatum) has been widely claimed to be effective as an antidepressant. The mechanism of action is unknown; and the active ingredient, if any, has not been ascertained [1]. Studies of extracts standardized for hypericin (one of the herb's constituents) have found it to be about twice as effective as a placebo. A few studies have found it somewhat more effective than a standard antidepressant. However, none of these studies lasted more than six weeks, which is not long enough to determine how long the herb would be effective or to detect any long-term adverse effects [2]. In addition, some of the studies were not well-designed [3,4]. In most of these studies, the diagnosis was not well established, the placebo response rate was lower than usually seen in such studies, the dosage of standard antidepressants was low, and the dosage of hypericin varied more than six-fold. [1]. No serious side effects were reported, but minor side effects include gastrointestinal discomfort, fatigue, dry mouth, dizziness, skin rash, and hypersensitivity to sunlight. However, in February 2000, British journal Lancet carried reports that St. John's wort could interfere with the effectiveness of an AIDS remedy (indinavir) [5]; an immunosuppressive drug (cyclosporin) used to protect patients after heart transplantation [6]; and an anticoagulant (warfarin) [7]. Based on this study and other reports in the medical literature, the FDA issued a Public Health Advisory stating:

St. John's wort appears to be an inducer of an important metabolic pathway, cytochrome P450. As many prescription drugs used to treat conditions such as heart disease, depression, seizures, certain cancers or to prevent conditions such as transplant rejection or pregnancy (oral contraceptives) are metabolized via this pathway, health care providers should alert patients about these potential drug interactions to prevent loss of therapeutic effect of any drug metabolized via the cytochrome P450 pathway [8].

St. John's wort should not be used by women who are pregnant or are breastfeeding. Nor should it be used together with standard antidepressants. The potency and purity of the preparations sold in the United States are unknown [1].

There is no published evidence that St. John's wort is effective against severe depression, which, in any case, should receive professional help. For mild depression, psychotherapy directed at resolving the cause of the depression might be more prudent.

The NIH Office of Alternative Medicine has funded a 3-year, $4.3-million clinical trial that will compare the effects of hypericum, a placebo, and a standard antidepressive drug on patients who are followed for up to six months [9]. The results are expected in the year 2002. Regardless of the outcome, however, another problem must be overcome before consumers could use St. John's wort effectively. A Good Housekeeping Institute analysis of six widely available St. John's wort supplement capsules and four liquid extracts revealed a lack of consistency of the suspected active ingredients, hypericin and pseudohypericin. The study found:

• A 17-fold difference between the capsules containing the smallest amount of hypericin and those containing the largest amount, based on manufacturer's maximum recommended dosage.
• A 13-fold difference in pseudohypericin in the capsules.
• A 7-to-8-fold differential from the highest to the lowest levels of liquid extracts [10].

A sinilar investigation by the Los Angeles Times found that 7 of10 products contained between 75% and 135% of the labeled hypericin level, and three contained no more than about half the labeled potency [11].

References

1. St. John's Wort. The Medical Letter 39:107-108, 1997.
2. Linde K and others. St. John's wort for depression -- an overview and meta-analysis of randomised clinical trials. British Medical Journal 313:253-258, 1996.
3. De Smet PAGM, Nolen WA. St. John's wort as an antidepressant: Longer term studies are needed before it can be recommended in major depression. British Medical Journal 313:241-242, 1996.
4. Gaster B, Holroyd J. St. John's wort in depression. Archives of Internal Medicine 160:152-156, 2000.
5. Piscitelli SC and others. Indinavir concentrations and St John's wort. Lancet 355:547, 2000.
6. Ruschitzka F and others. Acute heart transplant rejection due to Saint John's wort. Lancet 355:548, 2000.
7. Jobst KA and others. Safety of St John's wort. Lancet 355:576, 2000.
8. Lumpkin MM, Alpert S. Risk of drug interactions with St. John's wort and indinavir and other drugs. FDA Health Advisory, Feb 10, 2000.
9. St. John's wort study launched. Complementary and Alternative Medicine at the NIH 4(4):5, October 1997.
10. Good Housekeeping Institute. New Good Housekeeping Institute study finds drastic discrepancy in potencies of popular herbal supplement. News release, Consumer Safety Symposium on Dietary Supplements and Herbs, New York City, March 3, 1998.
11. Monmaney T. Labels' potency claims often inaccurate, analysis finds. Spot check of products finds widely varying levels of key ingredient. But some firms object to testing method and defend their brands' quality. Los Angeles Times, Aug 31, 1998.

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